Immune Function

The immune system is an intricate network of specialized tissues, organs, cells, and chemicals. The lymph nodes, spleen, bone marrow, thymus gland, and tonsils all play a role, as do lymphocytes (specialized white blood cells), antibodies, and interferon.

Two types of immunity protect the body: innate and adaptive. Innate immunity is present at birth and provides the first barrier against microorganisms. The skin, mucus secretions, and the acidity of the stomach are examples of innate immunity that act as barriers to keep unwanted germs away from more vulnerable tissues.

Adaptive immunity is the second barrier to infection. It is acquired later in life, such as after an immunization or successfully fighting off an infection. The adaptive immune system retains a memory of all the invaders it has faced. This is why people usually get the measles only once, although they may be repeatedly exposed to the disease. Unfortunately some bugs—such as the viruses that cause the common cold—“disguise” themselves and must be fought off time and again by the immune system.

For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

What are the symptoms of low immune function?

Symptoms of decreased immune function include frequent colds and flus, recurring parasitic infections, initially mild infections that become serious, opportunistic infections (infections by organisms that are usually well controlled by a healthy immune system, such as toxoplasmosis, cryptococcosis, and cytomegalovirus), and cancer.

Dietary changes that may be helpful for immune function

All forms of sugar (including honey) interfere with the ability of white blood cells to destroy bacteria.1 2 Animal studies suggest diets high in sucrose (table sugar) impair some aspects of immune function.3 4 The importance of these effects in the prevention of infections in humans remains unclear.

Alcohol intake, including single episodes of moderate consumption, interferes with a wide variety of immune defenses.5 6 Alcohol’s immune-suppressive effect may be one mechanism for the association between alcohol intake and certain cancers7 and infections.8 9 However, moderate alcohol consumption (up to three to four drinks per day) has been associated in preliminary studies with either no risk10 or a decreased risk for upper respiratory infections in young nonsmokers.11

The effect of fats on the immune system is complex and only partially understood. Excessive intake of total dietary fat impairs immune response, but some types of fat may be neutral or even beneficial.12 For example, monounsaturated fats, as found in olive oil, appear to have no detrimental effect on the immune system in humans at reasonable dietary levels.13

Research on the effect of the omega-3 fatty acids that are abundant in some fish, fish oils, and flaxseed oil is conflicting. Liquid diets containing omega-3 fatty acids used in hospitals for critically ill people have been shown to improve immune function and reduce infections.14 15 However, in one controlled study in healthy people, a low-fat diet improved or maintained immune function, but when fish was added to increase omega-3 fatty acid intake, immune function was significantly inhibited.16

Supplementation with DHA (an omega-3 fatty acid found in fish oil) in healthy young men has been shown to decrease the activity of immune cells, such as natural killer (NK) cells, and to inhibit certain measures of inflammation in the test tube.17 The anti-inflammatory effects of DHA may be useful in the management of autoimmune disorders; however, such benefits need to be balanced with the potential for increased risk of infections. Other studies suggest that increased oxidative damage might be the reason for the negative effects on the immune system sometimes caused by fish oil, and that increased intake of antioxidants, such as vitamin E, could correct the problem.18

As with omega-3 fatty acids, omega-6 fatty acids (as found in vegetable oils) have also produced conflicting effects on the immune system. Enriching a low-fat diet with omega-6 fatty acids did not impair immunity.19 However, diets high in omega-6 fatty acids have suppressed immunity in other reports.20 21

In summary, low-fat diets with moderate levels of monounsaturated fat from olive oil appear least likely to compromise immune function and may provide small benefits. Conclusions about the desirability of diets high in either omega-3 or omega-6 fatty acid supplementation await further research.

Many studies, in both animals and humans, have demonstrated immune-stimulating effects from yogurt which contains live cultures, such as Lactobacillus acidophilus and other probiotics (friendly bacteria). The effects of probiotics observed in humans include increasing the activity of several types of white blood cells. In preliminary human studies, consumption of live culture-containing yogurt has been associated with a reduced incidence of several immune-related diseases, including cancer, infections of the stomach and intestines, and some allergic reactions.22

Lifestyle changes that may be helpful for immune function

Both excessive thinness and severe obesity are associated with impaired immune responses.23 Obesity increases the risk of infection, at least in hospitalized patients, according to preliminary research.24 However, these effects may not occur with mild to moderate obesity in otherwise healthy people, and attempts to lose weight through dietary restriction may actually be harmful to the immune system.25 The detrimental effects of both excess weight and weight-loss diets appear to be offset when people regularly perform aerobic exercise.26 27

The effects of exercise on immune function depend on many factors, including frequency and intensity of exercise.28 Regular moderate physical activity has positive effects, at least on some measures of immunity, and has been shown to reduce risk of upper respiratory infection. However, very intense and prolonged exercise, such as running a marathon or overtraining, can, in the short term, actually increase the risk of developing infections.29 The positive effects of moderate exercise on immunity may also partly explain the apparent reduced susceptibility to cancer of physically active people.30

Nutritional supplements that may be helpful for immune function

Most,31 32 but not all,33 double-blind studies have shown that elderly people have better immune function and reduced infection rates when taking a multiple vitamin-mineral formula. In one double-blind trial, supplements of 100 mcg per day of selenium and 20 mg per day of zinc, with or without additional vitamin C, vitamin E, and beta-carotene, reduced infections in elderly people, though vitamins without minerals had no effect.34 Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.35 These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

Vitamin E enhances some measures of immune-cell activity in the elderly.36 This effect is more pronounced with 200 IU per day compared to either lower (60 IU per day) or higher (800 IU per day) amounts, according to double-blind research.37 Intakes under 200 IU per day have not boosted immune function in some reports.38

Beta-carotene and other carotenoids have increased immune cell numbers and activity in animal and human research, an effect that appears to be separate from their role as precursors to vitamin A.39 40 Placebo-controlled research has shown positive benefits of beta-carotene supplements in increasing numbers of some white blood cells and enhancing cancer-fighting immune functions in healthy people at 25,000–100,000 IU per day.41 42

In double-blind trials in the elderly, supplementation with 40,000–150,000 IU per day of beta-carotene has increased natural killer (NK) cell activity,43 but not several other measures of immunity.44

Controlled research has found that 50,000 IU per day of beta-carotene boosted immunity in people with colon cancer but in not those with precancerous conditions in the colon.45 Beta-carotene has also prevented immune suppression from ultraviolet light exposure.46 Effects on immunodefiency in HIV-positive people have been inconsistent using beta-carotene.47 48

Vitamin C stimulates the immune system by both elevating interferon levels49 and enhancing the activity of certain immune cells.50 51 Two studies came to opposite conclusions about the ability of vitamin C to improve immune function in the elderly,52 53 and two other studies did not agree on whether vitamin C could protect people from hepatitis.54 55 However, a review of 20 double-blind studies concluded that while several grams of vitamin C per day has only a small effect in preventingcolds, when taken at the onset of a cold, it does significantly reduce the duration of a cold.56 In controlled reports studying people doing heavy exercise, cold frequency was reduced an average of 50% with vitamin C supplements ranging from 600 to 1,000 mg per day.57 Thus, the overall effect of vitamin C on immune function is unclear, and its usefulness may vary according to the situation.

Vitamin A plays an important role in immune system function and helps mucous membranes, including those in the lungs, resist invasion by microorganisms.58 However, most research shows that while vitamin A supplementation helps people prevent or treat infections in developing countries where deficiencies are common,59 little to no positive effect, and even slight adverse effects, have resulted from giving vitamin A supplements to people in countries where most people consume adequate amounts of vitamin A.60 61 62 63 64 65 66 Moreover, vitamin A supplementation during infections appears beneficial only in certain diseases. An analysis of trials revealed that vitamin A reduces mortality from measles and diarrhea, but not from pneumonia, in children living in developing countries.67 A double-blind trial of vitamin A supplementation in Tanzanian children with pneumonia confirmed its lack of effectiveness for this condition.68 In general, parents in the developed world should not give vitamin A supplements to children unless there is a reason to believe vitamin A deficiency is likely, such as the presence of a condition causing malabsorption (e.g., celiac disease). However, the American Academy of Pediatrics recommends that all children with measles be given short-term supplementation with high-dose vitamin A in cases of hospitalization, malnutrition, and other special circumstances determined by a doctor.69

A combination of antioxidants vitamin A, vitamin C, and vitamin E significantly improved immune cell number and activity compared with placebo in a group of hospitalized elderly people.70 Daily intake of a 1,000 mg vitamin C plus 200 IU vitamin E for four months improved several measures of immune function in a preliminary study.71 To what extent immune-boosting combinations of antioxidants actually reduce the risk of infection remains unknown.

The amino acid glutamine is important for immune system function. Liquid diets high in glutamine have been reported in controlled studies to be more helpful to critically ill people than other diets.72 73 Endurance athletes are susceptible to upper respiratory tract infections after heavy exercise, which depletes glutamine levels in blood.74 Although the effects of glutamine supplementation on immune function after exercise have been inconsistent,75 76 a double-blind study giving athletes glutamine (2.5 grams after exercise and again two hours later) reported significantly fewer infections with glutamine.77

Supplements of probiotics (friendly bacteria) such as Lactobacillus acidophilus, or the growth factors that encourage their development in the gastrointestinal tract may help protect the body from harmful organisms in the intestine that cause local or systemic infection according to published research,78 79 including controlled80 trials. The effective amount of probiotics depends on the strain used, as well as the concentration of viable organisms. Infectious diarrhea in children has been successfully reduced with supplements of friendly bacteria in several trials, some of which were double-blind.81 82

The thymus gland is responsible for many immune system functions. Preliminary studies suggest that a thymus extract known as Thymomodulin® may improve immune function, and double-blind trials in children and adults with a history of recurrent respiratory-tract infections have found reduced numbers of recurrent infections with Thymomodulin supplementation.83 84 85 86 87 Thymomodulin has also been shown in a double-blind study to improve immune function in cases of exercise-induced immune suppression, and in preliminary studies to improve immune function in people with diabetes and in elderly people.88 89 90 91

Zinc supplements have been reported to increase immune function.92 93 This effect may be especially important in the elderly according to double-blind studies.94 95 Some doctors recommend zinc supplements for people with recurrent infections, suggesting 25 mg per day for adults and lower amounts for children (depending on body weight). However, too much zinc (300 mg per day) has been reported to impair immune function.96

While zinc lozenges have been shown to be effective for reducing the symptoms and duration of the common cold in some controlled studies, it is not clear whether this effect is due to an enhancement of immune function or to the direct effect of zinc on the viruses themselves.97

Large amounts of the carotenoid lycopene have been shown to increase the activity of NK cells in the elderly. In a controlled trial, 15 mg of lycopene significantly increased NK cell concentration, but no other immune functions.98

A deficiency of vitamin B12 has been associated with decreased immune function. In a controlled trial, people with vitamin B12 deficiency anemia were also found to have markedly decreased levels of white blood cells associated with immune function.99 Restoration of vitamin B12 stores by means of injections improved levels of these immune cells, suggesting an important role for vitamin B12 in immune function.

Beta-glucan is a fiber-type polysaccharide (complex sugar) derived from the cell wall of baker’s yeast, oat and barley fiber, and many medicinal mushrooms, such as maitake. Numerous experimental studies in test tubes and animals have shown beta-glucan to activate white blood cells.100 101 102 103 104 In fact, there have been hundreds of research papers on beta-glucan since the 1960s.105 The research indicates that beta-1,3-glucan, in particular, is very effective at activating white blood cells known as macrophages and neutrophils. A beta-glucan–activated macrophage or neutrophil can recognize and kill tumor cells, remove cellular debris resulting from oxidative damage, speed up recovery of damaged tissue, and further activate other components of the immune system.106 107 Although the research in test tube and animal studies is promising, many questions remain about the effectiveness of beta-glucan as an oral supplement to enhance immune function in humans. Controlled trials are necessary to determine whether humans can benefit from beta-glucan, and in what amounts oral beta-glucan must be taken from meaningful effects.

The hormone DHEA effects immunity. In a controlled trial, a group of elderly men with low DHEA levels who were given a high level of DHEA (50 mg per day) for 20 weeks, experienced a significant activation of immune function.108 Postmenopausal women have also shown increased immune functioning in just three weeks when given DHEA in double-blind research.109

The effects of eating fish and other dietary sources of omega-3 fatty acids is discussed above in the nutritional section. In terms of fish oil supplements, except for effects in hospitalized patients, most studies have reported that additional omega-3 intake decreases immune function.110 111 112 113 Antioxidants may correct this problem, according to preliminary research.114

Liquid diets containing supplemental arginine, omega-3 fatty acids, and nucleotides such as ribonucleic acid (RNA) have been more effective than other liquid diets in both maintaining immune function and reducing infections in critically ill and post-surgical hospital patients in most,115 116 117 118 119 but not all,120 121 double-blind trials. Typical daily intakes in these trials are 3.3 grams of omega 3 fatty acids, 12.5 grams of arginine, and 1.2 grams of RNA. No research has studied the effects of these supplements in people with less severe health problems.

A double-blind trial showed that 45 grams per day of whey protein increased blood glutathione levels in a group of HIV-infected people.122 Test tube123 124 and animal125 studies suggest that whey protein may improve some aspects of immune function.

Are there any side effects or interactions with immune function?

Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful for immune function

In general, human studies have found that echinacea taken orally stimulates the function of a variety of immune cells, particularly natural killer cells.126 The balance of evidence currently available from studies suggests that echinacea speeds recovery from the common cold, via immune stimulation (as opposed to killing the cold virus directly).127 Evidence on preventing the common cold with echinacea is largely negative, suggesting its immune-stimulating activity may be mild in generally healthy people. Other studies on oral echinacea have not found that it stimulates activity of the white blood cells known as neutrophils.128 Many doctors recommend 3–5 ml of tincture three times per day to improve immune function. Echinacea in capsule form is also commonly available.

Andrographis has been shown in a double-blind trial to successfully reduce the severity of the common cold.129 A preliminary study also suggests it may prevent the onset of a cold in healthy people.130 These actions are thought to be due to the immune system enhancing actions of the active constituents known as andrographolides.131

Asian ginseng has a long history of use in traditional herbal medicine for preventing and treating conditions related to the immune system. A double-blind study of healthy people found that taking 100 mg of a standardized extract of Asian ginseng twice per day improved immune function.132

Eleuthero (Siberian ginseng) has also historically been used to support the immune system. Preliminary Russian research has supported this traditional use.133 A double-blind study has shown that healthy people who take 10 ml of eleuthero tincture three times per day had an increase in certain T lymphocytes important to normal immune function. These effects have not been studied in people with lowered immune function. The amount of eleuthero used in this trial is exceptionally high, though no side effects were seen.

Ashwagandha is considered a general stimulant of the immune system,134 and has been called a tonic or adaptogen135 —an herb with multiple, nonspecific actions that counteract the effects of stress and generally promote wellness. More research is needed to better evaluate these claims.

Complex polysaccharides present in astragalus and in maitake and coriolus mushrooms appear to act as “immunomodulators” and, as such, are being researched for their potential role in AIDS and cancer. Presently, the only human studies on astragalus indicate that it can prevent white blood cell numbers from falling in people given chemotherapy and radiotherapy and can elevate antibody levels in healthy people.136 Maitake has only been studied in animals as a way to increase immune function.137 The primary immuno-activating polysaccharide found in these mushrooms, beta-D-glucan, is well absorbed when taken orally138 and is currently under investigation as a supportive tool for HIV infection. Results from future research will improve the understanding of the possible benefits of these mushrooms and their constituents.

Substances found in cat’s claw, called oxyindole alkaloids have been shown to stimulate the immune system.139 However, little is known about whether this effect is sufficient to prevent or treat disease.

Cordyceps has immune strengthening actions in human and animal studies.140 141 Further research is needed but it may be helpful in a wide range of conditions in which the immune system is weakened. The usual amount taken is 3 to 4.5 grams twice daily as capsules or simmered for 10 to 15 minutes in water for tea.

Green tea has stimulated production of immune cells and has shown anti-bacterial properties in animal studies.142 143 144 More research is needed to evaluate the effectiveness of green tea in protecting against infection and other immune system-related diseases.

Preliminary research suggests that fo-ti plays a role in a strong immune system and has antibacterial action.145 More research is needed to further understand the potential importance of these effects.

The main active compound in ligustrum is ligustrin (oleanolic acid). Studies, mostly conducted in China, suggest that ligustrum stimulates the immune system.146 Ligustrum is often combined with astragalus in traditional Chinese medicine. Although used for long-term support of the immune system in people with depressed immune function or cancer, more research is needed to demonstrate the optimal length of time to use ligustrum.

Animal and test tube studies show noni to have some immune-enhancing activity. Specifically, the polysaccharide component has been shown to increase the release of immune-enhancing compounds that activate white blood cells to destroy tumor cells.147 The usual recommendation is 4 ounces of noni juice 30 minutes before breakfast (effectiveness is thought to be best on an empty stomach). Human studies are needed to confirm the usefulness of noni.

Are there any side effects or interactions with immune function?

Refer to the individual herb for information about any side effects or interactions.

Holistic approaches that may be helpful for immune function

The immune system is suppressed during times of stress. Chronic mental and emotional stress can reduce immune function, but whether this effect is sufficient to increase the risk of infection or cancer is less clear.148 149 Nevertheless, immune function has been increased by stress-reducing techniques such as relaxation exercises, biofeedback, and other approaches,150 151 although not all studies have shown a significant effect.152

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